Articular cartilage protection in Ctsk-/- mice is associated with cellular and molecular changes in subchondral bone and cartilage matrix

Journal of Cellular Physiology
Fabiana N SokiHicham Drissi

Abstract

Osteoarthritis (OA) is a degenerative disease and a major cause of chronic disability in aging individuals. Cathepsin K (CatK), encoded by the Ctsk gene, has been implicated in the pathogenesis of pycnodysostosis and osteoporosis. The use of a selective inhibitor of CatK was recently shown to delay OA progression in rabbits. However, the cellular mechanisms underlying these protective effects remain unexplored. We examined articular cartilage maintenance and joint bone remodeling using Ctsk null mice (Ctsk-/- ) which underwent destabilization of the medial meniscus (DMM). We found that Ctsk-/- mice displayed delayed remodeling of subchondral and calcified cartilage by osteoclasts and chodroclasts respectively in DMM-induced osteoarthritis. While WT mice displayed a more severe OA phenotype than Ctsk-/- mice at 16 weeks, higher subchondral bone volume and lower trabecular spacing were also observed in surgically-induced OA joints of Ctsk-/- mice. However, no differences were seen in non-surgical controls. During OA progression, TRAP+ osteoclast numbers were increased in both WT and Ctsk-/- mice. However, Ctsk-/- mice had fewer physis-derived chondroclasts than WT when OA was present. These data suggest that CatK may differential...Continue Reading

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Citations

Jan 17, 2020·Molecular Genetics & Genomic Medicine·Ehsan RazmaraMasoud Garshasbi
Feb 9, 2021·Frontiers in Cell and Developmental Biology·Xiaobo ZhuYangzi Jiang
Oct 31, 2020·Nature Reviews. Rheumatology·Augustin LatourtePascal Richette
Jul 3, 2021·International Journal of Molecular Sciences·Roxanne N StoneJulia Thom Oxford

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